PRIMING EFFECT OF LUTEINIZING HORMONE RELEASING FACTOR ELICITED BY PREOPTIC STIMULATION AND BY INTRAVENOUS INFUSION AND MULTIPLE INJECTIONS OF THE SYNTHETIC DECAPEPTIDE

1976 ◽  
Vol 69 (3) ◽  
pp. 359-372 ◽  
Author(s):  
G. FINK ◽  
S. A. CHIAPPA ◽  
M. S. AIYER

SUMMARY We have investigated whether the priming effect of LH-RF can be elicited by electrical stimulation of the medial preoptic area, or by i.v. infusion or multiple i.v. injections of the synthetic decapeptide. All experiments were carried out on animals anaesthetized with sodium pentobarbitone at 13.30 h. In pro-oestrous rats, the LH response to the second of two electrical stimuli, 15 min in duration and separated by 60 min, was significantly greater than the response to the first stimulus. When synthetic LH-RF was infused at a constant rate for 90 min, plasma LH increased gradually for the first 45–60 min after which it increased markedly. This enhanced secretion of LH did not occur in rats which were infused with the same total dose of LH-RF, either 15 or 75 ng/100 g body wt, over periods of 45 min or less. When a dose of 15 ng LH-RF/100 g body wt was administered in six divided doses by i.v. injections, each separated by 15 min, there was a marked increase in plasma LH after 75 min. The profile of the mean plasma LH concentration in rats subjected to preoptic stimulation for 90 min was similar to that in rats infused for 90 min with LH-RF, but the variation in response was much greater in the stimulated rats. These results indicate that the priming effect can be elicited by endogenous as well as synthetic LH-RF, and that whether LH-RF reaches the pituitary at a constant rate or in a pulsatile manner the factor is capable of significantly increasing the responsiveness of the gonadotrophs. The relevance of these findings with respect to the development of the spontaneous preovulatory LH surge is discussed. A priming effect could not be elicited by constant LH-RF infusion in dioestrous rats; this supports the view that steroid hormones, especially oestradiol-17β, determine the magnitude of the effect. The LH response in male rats subjected to i.v. infusion of LH-RF was much lower than in females. Pre-treatment with oestradiol benzoate did not increase the response significantly, suggesting that this sex difference cannot be ascribed simply to low levels of plasma oestrogen in the male.

1966 ◽  
Vol 51 (2) ◽  
pp. 281-289 ◽  
Author(s):  
J. Moll ◽  
G. H. Zeilmaker

ABSTRACT Castrated young adult inbred male rats bearing ovarian transplants were subjected to electrical stimulation of the hypothalamus. This was done in order to investigate whether discharge of ovulatory amounts of gonadotrophins could be induced in such male animals by this procedure. Bilateral stimulations with unipolar electrodes and a DC current of 1.5 mA applied during 10 seconds induced in the ovarian grafts histological changes indicating the discharge of ovulatory amounts of gonadotrophins. In animals killed one day after stimulation these changes consisted of displacement of the ova towards the centre of the follicles with loosening of the cumulus oophorus. In one animal the ova had left the follicles. In animals killed three days after stimulation numerous young corpora lutea could be observed. These results were obtained with electrode tips either close to the median eminence, or in the preoptic area. Shamstimulations were ineffective. Some of the experimental animals received progesterone pretreatment. This rendered the stimulations ineffective, if continued until the day preceding stimulation, but seemed without effect on the results of stimulation, if two or three days without progesterone preceded the stimulations.


1977 ◽  
Vol 86 (4) ◽  
pp. 728-732 ◽  
Author(s):  
Y. Epstein ◽  
B. Lunenfeld ◽  
Z. Kraiem

ABSTRACT The aim of this study was to investigate effects of androgens on gonadotrophin release in response to gonadotrophin-releasing hormone (Gn-RH) stimulation in vitro. Hemipituitaries of mature male rats were pre-incubated for 90 min with T, DHT, 3α- or 3β-diol (4 ng or 4 μg/ml medium), and the incubation continued for 240 min after adding Gn-RH (1 ng/ml medium). Gn-RH caused a 4-5-fold rise in the secretion of LH and a 2-fold rise in FSH secretion. The effect of the androgens was dose-dependent. At low levels, T and DHT exerted no effect on Gn-RH-stimulated gonadotrophin release, whereas the two androstanediols (3α- and 3β-diol) augmented the Gn-RH stimulation of both gonadotrophins, though preferentially LH. With high doses of androgens, the results obtained showed: a) no effect of T; b) DHT suppression of the Gn-RH-stimulated FSH release; c) suppression of Gn-RH stimulation by 3α- and 3β-diol regarding both LH and FSH. It is concluded that T exerts through its reduced metabolites a feedback effect on the pituitary gland responsiveness to Gn-RH stimulation.


1973 ◽  
Vol 58 (2) ◽  
pp. 163-176 ◽  
Author(s):  
M. E. VELASCO ◽  
I. ROTHCHILD

SUMMARY Factors affecting luteinizing hormone (LH) secretion in response to stimulation of the preoptic area (POA) of the forebrain in rats were explored by determining serum LH levels after electrochemical stimulation of the POA. In rats made anovulatory by exposure to constant light (CLA rats), peak concentrations of LH in serum were found 2 h after stimulation with 5–15 mC, and 1 h after stimulation with 0·5–1 mC. The peak levels increased with increasing doses between 0·5 and 15 mC. The incidence of rats ovulating and the mean number of ovulations/rat were roughly proportional to the stimulating dose, but a plateau was reached between 5 and 10 mC. A threshold level of serum LH seemed to be necessary for ovulation, and the incidence of ovulations of six ova or more/rat increased with the increase in peak serum LH level. Preoptic-roof section, which cuts dorsal afferents to the POA, enhanced the increase in serum LH in response to POA stimulation in CLA rats, while sodium pentobarbitone anaesthesia decreased the response. In both cases, the incidence of ovulation and the number of ovulations/rat were not different from values found in POA-stimulated control CLA rats showing the same peak serum LH level. In normal cyclic rats the response of serum LH to stimulation was much greater on the morning of pro-oestrus than on that of oestrus; at prooestrus a second rise occurred between 17.00 and 19.00 h. Three days after ovariectomy the basal level of LH increased; these ovariectomized rats showed a small increase in response to a dose of 5 mC. Treatment with 20 μg oestradiol benzoate at the time of ovariectomy, however, resulted in a lowered basal LH level, but the peak response to 5 mC was almost as great as that found in similarly stimulated intact CLA rats. In intact males and in neonatally androgen-treated females the peak levels of serum LH in response to doses of 5 or 15 mC were equivalent to those in CLA females in response to doses of only 1–5 mC.


1976 ◽  
Vol 68 (1) ◽  
pp. 57-70 ◽  
Author(s):  
M. G. JAMIESON ◽  
G. FINK

SUMMARY The release of LH and FSH after the application of an electrical stimulus to the anterior diencephalon of male rats has been studied. The stimulus was applied through either platinum or steel electrodes implanted stereotaxically in animals anaesthetized with urethane. The efficacy of various parameters of stimulation by means of a current consisting of balanced biphasic square waves, was tested by systematically changing the frequency, amplitude and duration of the pulses. The effect of direct current (d.c.) stimulation on hormone release was also examined. The concentrations of the hormones in blood withdrawn from the femoral vein before and at frequent intervals up to 80 min after application of the stimulus were determined by radioimmunoassay. The optimal parameters for the release of LH by square wave stimulation of the medial preoptic area were: frequency, 60 Hz; pulse amplitude, 0·50 mA; pulse duration, 1·00 ms. This stimulus was more effective when applied through steel than through platinum electrodes. Direct current stimulation (15 μA for 10 s) through steel electrodes was most effective of all. When applied through platinum electrodes to the medial preoptic and anterior hypothalamic areas, the optimal square wave stimulus produced significant increases in the concentration of LH after 5 and 10 min respectively. The concentration of plasma FSH in these animals also increased, but the increments were much less than the increments in LH. The magnitude of the respective increases of the gonadotrophins after stimulation of the two brain areas did not differ significantly. Measurement of the milk ejection response to stimulation of the hypothalamo-hypophysial tract in a lactating rat indicated that the spread of the square wave stimulus was no more than 1·5 mm from the electrode tip. The significance of these findings is discussed with respect to the importance of the medial preoptic area in the male rat, the neurones which may be involved in the regulation of gonadotrophin secretion, and the parameters of stimulation used in studying the hypothalamo-hypophysial system.


1981 ◽  
Vol 97 (3) ◽  
pp. 297-304
Author(s):  
Jørgen Warberg

Abstract. The prostaglandin (PG) analogue 7-oxa-13-prostynoic acid (7-OPA) was infused into a lateral ventricle of the brain of adult male rats and the effect of the analogue on a subsequent stimulation of LH release by intraventricular infusion of PG's was determined. Pre-treatment of the animals with 44–132 μg of 7-OPA potentiated the stimulatory effect of 2 μg PGE2 on the release of LH but the analogue alone had no effect on the hormone secretion. The minimal effective dose of PGE2 was determined to be within the range 0.01–0.05 μg and it was found that priming with 132 μg of 7-OPA caused a formerly sub-threshold dose (0.01 μg) of PGE2 to become an effective stimulus for the release of LH. In contrast to its potentiating effect on PGE2-induced LH release 7-OPA did not alter the stimulatory action of PGF2α (2 μg) on the secretion of LH. 7-OPA had no effect on LRH-induced release of LH indicating that the PG analogue acts at a suprapituitary site to enhance PGE2-induced LH release. The potentiating effect of 7-OPA may be exerted at a binding site for PGE2 in the brain and the results suggest the existence of a different binding site for PGF2α. The possibility also exists that 7-OPA inhibit metabolic inactivation of PGE2.


2000 ◽  
Vol 278 (3) ◽  
pp. H964-H970 ◽  
Author(s):  
Yoshikazu Sato ◽  
George J. Christ

Recent findings indicate a complex role for the medial preoptic area (MPOA) in modulating penile erection. To further investigate this important area we measured changes in intracavernous pressure (ICP) elicited by electrical stimulation of the MPOA and evaluated the contribution of the cavernous nerve to the ICP responses after bilateral transection of the cavernous nerve (CN). In all experiments electrical stimulation was performed unilaterally in anesthetized male rats. Two distinct patterns of ICP response were seen after electrical stimulation of the MPOA: 1) increases in ICP during electrical stimulation ( pattern 1, n = 10 rats) and 2) increases in ICP after electrical stimulation was terminated ( pattern 2, n = 10 rats). For pattern 1, increases in ICP during stimulation exhibited a stable plateau without contraction of striated penile muscles, and bilateral transection of the CN eliminated the ICP responses. For pattern 2, increases in ICP observed after stimulation were lower, more variable, and accompanied by significant amplitude variations (“peaks”), caused by contraction of striated penile muscles. Bilateral transection of the CN eliminated the pattern 2 ICP response but did not alter striated muscle contraction. Histological studies documented that pattern 1 and pattern 2 responses occurred via electrical stimulation of the anterior and posterior areas of the MPOA, respectively. Thus both responses appear to result from activation of the CN, but the pattern 2 response apparently involves contraction of the striated penile muscles as well.


1972 ◽  
Vol 54 (2) ◽  
pp. 227-237 ◽  
Author(s):  
H. G. BURGER ◽  
G. FINK ◽  
V. W. K. LEE

SUMMARY The presence of luteinizing hormone releasing factor (LH-RF) activity was investigated in pituitary stalk and systemic blood collected from rats ovariectomized at least 3 weeks previously, and in stalk blood from male rats in which electrodes had been implanted in the medial preoptic area of the brain. Most of the assayable luteinizing hormone (LH) present in the blood samples was eliminated by acid-ethanol extraction followed by ultrafiltration. The ultrafiltrates were injected into ovariectomized rats treated with oestrogen and progesterone, and increments in the concentration of LH in the sera of these animals, estimated by radioimmunoassay, were taken as an indication that the filtrate was able to release LH from the anterior pituitary gland. The ultrafiltrates of both the stalk and systemic plasma from the ovariectomized rats exhibited LH-RF activity as did the ultrafiltrates of blood collected from the pituitary stalk of the male rats during electrical stimulation of the preoptic area; stalk blood collected from these animals before the current was applied appeared to be inactive. The LH-RF activity of the ultrafiltrates of systemic and pituitary stalk plasma taken from ovariectomized rats was similar, and, therefore, the possibility is raised that the response of the pituitary glands in ovariectomized rats treated with oestrogen and progesterone is of an all or none type. The presence of appreciable quantities of LH-RF in the systemic plasma of ovariectomized rats may explain the discrepancy between bioassay and immunoassay estimates of LH in the plasma of these animals. The rapid increase in the concentration of serum LH and in the LH-RF activity of pituitary stalk plasma which followed stimulation of the preoptic area suggests that this region of the brain may be important in the control of the secretion of LH in the male as well as in the female animal.


1982 ◽  
Vol 99 (2) ◽  
pp. 195-199 ◽  
Author(s):  
T. R. Koiter ◽  
N. Pols-Valkhof ◽  
G. A. Schuiling

Abstract. The influence of an LRH injection (50 ng/ 100 g b.w.) on the LH-response to a second, equally large LRH injection or a constant rate infusion of LRH (104 ng/h), administered 1 h later, was studied in phenobarbitone-anaesthetized, oil- or oestradiol benzoate (OeB)-treated rats ovariectomized (OVX) 5 weeks earlier. From the plasma LH concentration the mean maximal LH secretion rates, as well as the amounts of LH secreted, were calculated on the basis of a one-compartment model, proceeding from a half-life of LH of 15 min. In both the oil- and the OeB-treated animals, not only the mean maximal LH secretion rate, but also the amount of LH secreted during the first hour following the injection, was significantly higher after the second LRH injection than after the first one (LRH self-priming effect). Infusion of LRH in LRH-primed OVX rats revealed that the LH secretion accelerates immediately after the start of the infusion and this acceleration lasts about 1 h. In the saline-injected controls, on the other hand, the LH secretion, although elevated, remains constant during the first 30 min of LRH infusion and accelerates only thereafter during about 1 h. Yet, maximal LH secretion rates are not statistically different between the LRH-primed oil- or OeB-treated OVX rats and their respective saline-injected controls. It is concluded that the self-priming effect of LRH does not lead to an increase of the ultimate maximal LH secretion rate. Rather, during priming the conditions necessary for immediate acceleration of the LH secretion rate are established, and priming thus causes a shift in time, that is, an advancement, of the LH-response to a subsequent LRH stimulus.


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